Thalamocortical Connectivity In Autism Spectrum Disorder: A Probabilistic DTI Tractography Study

Background: A number of studies have shown abnormal volume, neuronal integrity, perfusion, and metabolism of the thalamus in autism spectrum disorder (ASD). However, evidence on thalamocortical connectivity remains scant, except for a few functional studies. This lack of evidence is surprising, given the important role of thalamocortical connectivity in cortical functional specialization and differentiation, which are generally thought to be affected in ASD.

Objectives: We assessed the integrity of connections between thalamus and cortex in children and adolescents with ASD, using probabilistic diffusion tensor imaging (DTI) tractography. 

Methods: DTI data from 17 children with ASD and 17 typically developing (TD)children were acquired from a 3T MRI scanner using single-shot diffusion-weighted EPI pulse sequence with two degrees of diffusion weighting (b=0 and 2000 s/mm², 15 non-linear directions, four repetitions). Geometric distortions due to local magnetic field inhomogeneities were corrected using field maps. The PickAtlas SPM toolbox was used to obtain white matter masks for thalamus, and fronto-temporal and parieto-occipital cortices from the standard MNI brain template. Tracts were derived for pairs between thalamus and frontal/temporal and parietal/occipital white matter regions-of-interest (ROIs). Bayesian estimation of diffusion parameters using Markov Chain Monte Carlo sampling techniques and trilinear interpolation of the probability density functions were employed to determine the streamline between given ROI pairs using probabilistic tractography toolbox in FSL software. Fractional anisotropy (FA) values of identified tracts were determined.   

Results: FA of thalamocortical projections to and from the fronto-temporal cortex was significantly reduced in the ASD group compared to the TD group in both hemispheres (left hemisphere: 0.25±0.05 for ASD group versus 0.36±.04 for TD group, p=0.03; right hemisphere: 0.26±0.05 for ASD group versus 0.34±0.03 for TD group, p=0.04). For connections between thalamus and parieto-occipital cortex, the difference in FA was marginally significant (p=.08) in both hemispheres. No significant group differences in hemispheric asymmetry were found.

Conclusions: These results suggest that abnormalities in thalamocortical fiber tracts are present in children and adolescents with ASD. They add anatomical support for a few previous findings of impaired functional thalamocortical connectivity. Findings of white matter compromise were significant for thalamic connections with fronto-temporal cortex, but less robust for parieto-occipital cortex, consistent with evidence of severe white matter growth anomalies in frontal lobe, but relative sparing of occipital lobe. A follow-up study examining thalamocortical connectivity at higher resolution is underway.

Funding: R01-MH081023